Anoikis is a type of programmed cell death induced by detachment from the extracellular matrix. In cancer cells, anoikis resistance is essential for cancer cell survival in blood circulation and distant metastasis. However, the mechanisms behind anoikis resistance of gastric cancer remain largely unknown. Herein, we demonstrate that NADPH oxidase 4 (NOX4) expression and reactive oxygen species (ROS) generation are upregulated in suspension gastric cell cultures compared with adherent cultures. Silencing of NOX4 decreases ROS generation and downregulates EGFR, sensitizing cells to anoikis. NOX4 overexpression upregulates ROS and EGFR levels and promotes anoikis resistance. NOX4 depletion inhibits gastric cancer survival in blood circulation and attenuates distant metastasis. NOX4 expression is correlated with EGFR expression in patients. In conclusion, induction of NOX4 expression by detachment promotes anoikis resistance of gastric cancer through ROS generation and downstream upregulation of EGFR, which is critical for the metastatic progression of gastric cancer.

The protein tyrosine phosphatase PTP1B, which is encoded by PTPN1, is a ubiquitously expressed nonreceptor protein tyrosine phosphatase. PTP1B has long been known to negatively regulate insulin and leptin receptor signalling. Recently, it was reported to be aberrantly expressed in cancer cells and to function as an important oncogene. In this study, we found that PTP1B protein levels are dramatically increased in breast cancer (BC) tissues and that PTP1B promotes the proliferation, and suppresses the apoptosis, of both HER2‐positive and triple‐negative BC cell lines. Bioinformatics analysis identified that the miRNA, miR‐193a‐3p, might potentially target PTP1B. We demonstrate that miR‐193a‐3p regulates PTP1B in BC cells and that it regulates the proliferation and apoptosis of BC cells by targeting PTP1B, both in vitro and in vivo. In conclusion, this study confirms that PTP1B acts as an oncogene in BC and demonstrates that miR‐193a‐3p can serve as a tumour suppressor gene in BC by targeting PTP1B.

MicroRNAs (miRNAs) play an important role in the regulation of human cancers, including breast cancer (BC). In the current study, we examined the expression pattern of the miRNA miR‐125a‐5p in human BC tissues, tumorigenesis of BC progression. We found that miR‐125a‐5p was significantly downregulated in human BC tissues. Overexpression of miR‐125a‐5p in a xenograft mouse model indicated that miR‐125a‐5p may function as a tumour suppressor during carcinogenesis. To explore the molecular mechanism by which miR‐125a‐5p contributes to BC progression, we predicted the target genes of miR‐125a‐5p and identified BC susceptibility gene 1–associated protein 1 (BAP1) as a direct target. Finally, we demonstrated that BAP1 had opposing effects to those of miR‐125a‐5p on BC cells, suggesting that miR‐125a‐5p may inhibit cell proliferation and promote cell apoptosis by negatively regulating BAP1. Taken together, our findings provide the first clues regarding the role of miR‐125a‐5p as a tumour suppressor in BC via the inhibition of BAP1 translation.

No abstract